1. Field of the Invention
The present invention relates generally to apparatus and method for taking the derivative of an electrical signal, and more particularly to apparatus and method for providing maximum slope of a slowly varying signal representative of organic cell osmotic fragility.
2. Description of Prior Art
In general, circuitry for taking the derivative of an electrical signal is known. For example, the prior art capacitor-resistor network known as a high pass filter is used for differentiating an electrical signal to an approximation. This prior art circuit is particularly useful where "fast" signals are being operated upon since required component values and physical size are compatable with other electronic and mechanical design constraints. This prior art circuit generally does not work well with slowly varying signals, for example, signals varying less than one volt per minute over perhaps an eight minute period.
A prior art circuit for providing the derivative of a slowly varying signal uses measurements of voltage increments over a plurality of equal time intervals. Obtaining equal intervals is sometimes a serious problem. This type of circuit samples and holds each measurement for a respective interval, after which interval the stored sample is compared with the instantaneous value of the signal. The information obtained is the desired slope, .DELTA. v/.DELTA. t.) This circuit has limitations for slowly varying signals, similar to those being operated upon by the present invention, one of the limitations occurring near zero signal value. At this extreme, small inherent offset errors are added to the storage signal which can cause large errors in the construction of the derivative signal. Also, filtering is required to remove step transitions, and this is not wholly successful under all conditions. Moreover, during a sampling period the circuit tends to be sensitive to noise spikes.
The present invention provides apparatus and method for accurately taking a derivative of an electrical signal including a slowly varying electrical signal, without the shortcomings of the prior art. The present invention does not require the cumbersome prior art incremental measurement of signal voltage, but employs high gain operational amplifiers and other circuitry in a novel arrangement that elegantly solves prior art problems of taking a derivative of a slowly varying signal. The present invention can be used in almost any application where a derivative of a slowly varying signal is desired, and finds particular utility with electromedical apparatus for measuring osmotic fragility of red blood cells. This measurement is made over an approximate 8-minute period in certain cases. The present invention provides to a physician or other observor exact information as to when maximum rate of change of percentage hemolysis of the blood cells occurs with respect to tonicity of suspension of the medium in which the blood cells are suspended.
With regard to specific application of this circuitry in the above-identified blood analyzing apparatus, background information is presented as follows. Red blood cells, called erythrocytes, are suspended in a liquid medium of lower than isotonic salt concentration, and absorb the low tonicity liquid by osmosis through cell membranes. At some osmotic gradient determined by tonicity of the suspension medium, sufficient pressure is developed within the cells to either burst their membranes or to open numerous pores therein which release hemoglobin into the surrounding medium. This action is commonly referred to as hemolysis. It is a function of condition of cell membrane and of salt concentration (tonicity of cell suspension medium), both of which are variable. The former can be determined through the latter.
Hemolysis is induced by rendering the suspension medium hypotonic. With knowledge of condition (concentration of salt) of the suspension medium that is required to reduce or start hemolysis and that required to complete hemolysis, an indication of the condition of the cell membranes is thought to be given. This, in turn, has been interpreted to be an indication of the health of the host.
In a report by Danon et al., entitled "Simple Rapid Osmotic Fragility Test Proposed as a Routine in Blood Banks" taken from Transfusion, Vol. 4, Number 5 (1964), pages 339-342, it is disclosed that the osmotic fragility curve and/or its derivative curve (rate of osmotic fragility) are useful tools for determining the acceptability of stored blood for transfusions. It is in the generation of this derivative curve that the present invention finds particular use. The authors of this report suggest that these osmotic fragility curves may be useful tools for determining acceptable blood donors, and it is in connection with this aspect of blood analysis that the present invention finds outstanding utility.
Other background information pertaining to this technology may be obtained from U.S. patent application Ser. No. 499,004, filed Aug. 20, 1974 in the name of Gabriel G. Nahas, and U.S. Pat. No. 3,605,539 to M. L. Polanyi, et al. both patent properties assigned to the assignee of the present invention and both incorporated herein by reference.